Ethyl 1-(4-methoxyphenyl)-4-nitropyrazole-3-carboxylate | 1190305-98-6

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 英文名称: Ethyl 1-(4-methoxyphenyl)-4-nitropyrazole-3-carboxylate
• CAS: 1190305-98-6
• 化学式: C₁₃H₁₃N₃O₅
• 分子量: 291.263
• InChiKey: RWZHGJIASYJHGY-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.2
• 重原子数：
  21
• 可旋转键数：
  5
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.23
• 拓扑面积：
  99.2
• 氢给体数：
  0
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  Ethyl 1-(4-methoxyphenyl)-4-nitropyrazole-3-carboxylate 在 palladium 10% on activated carbon 、 ammonium acetate 、 氨 、 环己烯 、 三氯氧磷 作用下， 以 乙醇 、 水 为溶剂， 反应 24.89h， 生成 2-(4-Methoxyphenyl)-5-methylpyrazolo[4,3-d]pyrimidin-7-amine
  参考文献：
  名称：

  2-Arylpyrazolo[4,3-d]pyrimidin-7-amino Derivatives As New Potent and Selective Human A₃ Adenosine Receptor Antagonists. Molecular Modeling Studies and Pharmacological Evaluation

  摘要：

  On the basis of our previously reported 2-arylpyrazolo[4,3-d]pyrimidin-7-ones, a set of 2-arylpyrazolo[4,3- d]pyrimidin-7-amines were designed as new human (h) A(3) adenosine receptor (AR) antagonists. Lipophilic groups with different steric bulk were introduced at the 5-position of the bicyclic scaffold (R-5 = Me, Ph, CH2Ph), and different acyl and carbamoyl moieties (R-7) were appended on the 7-amino group, as well as a para-methoxy group inserted on the 2-phenyl ring. The presence of acyl groups turned out to be of paramount importance for an efficient and selective binding at the hA(3) AR In fact, most of the 7-acylamino derivatives showed low nanomolar affinity (K-l, = 2.5-45 nM) and high selectivity toward this receptor. A few selected pyrazolo[4,3-d]pyrimidin-7-amides were effective in counteracting oxaliplatin-induced apoptosis in rat astrocyte cell cultures, an in vitro model of neurotoxicity. Through an in silica receptor-driven approach the obtained binding data were rationalized and the molecular bases of the observed hA(3) AR affinity and hA(3) versus hA(2A) AR selectivity were explained.

  DOI：

  10.1021/jm400068e
• 作为产物：
  描述：

  1-二甲基氨基-2-硝基乙烯 、 [(4-甲氧基苯基)肼基]氯乙酸乙酯 在 三乙胺 作用下， 以 氯仿 为溶剂， 反应 48.0h， 以25%的产率得到Ethyl 1-(4-methoxyphenyl)-4-nitropyrazole-3-carboxylate
  参考文献：
  名称：

  2-Phenylpyrazolo[4,3-d]pyrimidin-7-one as a New Scaffold To Obtain Potent and Selective Human A₃ Adenosine Receptor Antagonists: New Insights into the Receptor−Antagonist Recognition

  摘要：

  A molecular simplification approach of previously reported 2-arylpyrazolo[3,4-c]quinolin-4-ones was applied to design 2-arylpyrazolo[4,3-d]pyrimidin-7-one derivatives as new human A(3) adenosine receptor antagonists. Substituents with different lipophilicity and steric hindrance were introduced at the 5-position of the bicyclic Scaffold (R-5 = H, Me, Et, Ph, CH2Ph) and on the 2-phenyl ring (OMe, Me). Most of the synthesized derivatives were highly potent hA(3) adenosine receptor antagonists, the best being the 2-(4-methoxyphenyl)pyrazolo[4,3-d]pyrimidin-7-one (K-i = 1.2 nM). The new compounds were also highly selective, being completely devoid of affinity toward hA(1), hA(2A), and hA(2B) adenosine receptors. On the basis of the recently published human A(2A) receptor crystallographic information, we propose it novel receptor-driven hypothesis to explain both A(3) AR affinity and A(3) versus A(2A) Selectivity profiles of these new antagonists.

  DOI：

  10.1021/jm900718w